IL-12-independent LIGHT signaling enhances MHC class II disparate CD4 + T cell alloproliferation, IFN-γ responses, and intestinal graft-versus-host disease

Geri R. Brown, Edward L. Lee, Jihad El-Hayek, Katherine Kintner, Cheryl Luck

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Abstract

Inhibition of LIGHT (a cellular ligand for herpes virus entry mediator and lymphotoxin receptor)/herpes simplex virus entry mediator (HVEM) and LIGHT/lymphotoxin β receptor (LTβR) interactions decreases mortality in MHC class I and II disparate graft-vs-host disease (GVHD). The present studies assessed the effects of these interactions on the generation of CD4 + T cell alloresponses in MHC class II-disparate MLC and GVHD. An inhibitor protein of LIGHT and LTαβ2 (LTβR-Ig) and an inhibitor protein of LIGHT (HVEM-Ig) caused similar decreases in alloresponses of control B6 or B6.129S1-IL12rb2tm1Jm (B6.IL12R-/-) spleen cells (SpC) in a MHC class II-disparate MLC. GVHD-induced wasting disease in MHC class II-disparate recipients of B6 CD4+ SpC who received either the LTβR-Ig-encoding adenovirus (LTβR-Ig Adv; 13.1 ± 10.9%; n = 10; p = 0.0004) or the HVEM-Ig-encoding adenovirus (HVEM-Ig Adv; 16.4 ± 9.9%; n = 13; p = 0.0008) was significantly reduced compared with that in recipients of a control adenovirus (30.4 ± 8.8%; n = 13). Furthermore, gut GVHD histologic scores of recipients of B6 CD4+ SpC who received the LTβR-Ig Adv (0.8 ± 0.8; n = 5; p = 0.0007) or the HVEM-Ig Adv (1.4 ± 0.5; n = 5; p = 0.008) were reduced compared with scores of recipients of a control adenovirus (2.5 ± 0.75; n = 11). In the intestine, both LTβR-Ig Adv and HVEM-Ig Adv decreased CD4+ T cells (0.35 ± 0.4 × 106 (n = 6) vs 0.36 ± 0.02 × 106 (n = 9); p = 0.03 and p = 0.007) compared with control adenovirus (0.86 ± 0.42 × 106; n = 9). LIGHT is critical for optimal CD4+ T cell alloresponses in MHC class II-disparate MLC and GVHD.

Original languageEnglish (US)
Pages (from-to)4688-4695
Number of pages8
JournalJournal of Immunology
Volume174
Issue number8
StatePublished - Apr 15 2005

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Lymphotoxin-alpha
Virus Internalization
Graft vs Host Disease
Interleukin-12
Simplexvirus
T-Lymphocytes
Light
Tumor Necrosis Factor Ligand Superfamily Member 14
Adenoviridae
Spleen
Wasting Syndrome
Intestines
Ligands
Mortality

ASJC Scopus subject areas

  • Immunology

Cite this

IL-12-independent LIGHT signaling enhances MHC class II disparate CD4 + T cell alloproliferation, IFN-γ responses, and intestinal graft-versus-host disease. / Brown, Geri R.; Lee, Edward L.; El-Hayek, Jihad; Kintner, Katherine; Luck, Cheryl.

In: Journal of Immunology, Vol. 174, No. 8, 15.04.2005, p. 4688-4695.

Research output: Contribution to journalArticle

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title = "IL-12-independent LIGHT signaling enhances MHC class II disparate CD4 + T cell alloproliferation, IFN-γ responses, and intestinal graft-versus-host disease",
abstract = "Inhibition of LIGHT (a cellular ligand for herpes virus entry mediator and lymphotoxin receptor)/herpes simplex virus entry mediator (HVEM) and LIGHT/lymphotoxin β receptor (LTβR) interactions decreases mortality in MHC class I and II disparate graft-vs-host disease (GVHD). The present studies assessed the effects of these interactions on the generation of CD4 + T cell alloresponses in MHC class II-disparate MLC and GVHD. An inhibitor protein of LIGHT and LTαβ2 (LTβR-Ig) and an inhibitor protein of LIGHT (HVEM-Ig) caused similar decreases in alloresponses of control B6 or B6.129S1-IL12rb2tm1Jm (B6.IL12R-/-) spleen cells (SpC) in a MHC class II-disparate MLC. GVHD-induced wasting disease in MHC class II-disparate recipients of B6 CD4+ SpC who received either the LTβR-Ig-encoding adenovirus (LTβR-Ig Adv; 13.1 ± 10.9{\%}; n = 10; p = 0.0004) or the HVEM-Ig-encoding adenovirus (HVEM-Ig Adv; 16.4 ± 9.9{\%}; n = 13; p = 0.0008) was significantly reduced compared with that in recipients of a control adenovirus (30.4 ± 8.8{\%}; n = 13). Furthermore, gut GVHD histologic scores of recipients of B6 CD4+ SpC who received the LTβR-Ig Adv (0.8 ± 0.8; n = 5; p = 0.0007) or the HVEM-Ig Adv (1.4 ± 0.5; n = 5; p = 0.008) were reduced compared with scores of recipients of a control adenovirus (2.5 ± 0.75; n = 11). In the intestine, both LTβR-Ig Adv and HVEM-Ig Adv decreased CD4+ T cells (0.35 ± 0.4 × 106 (n = 6) vs 0.36 ± 0.02 × 106 (n = 9); p = 0.03 and p = 0.007) compared with control adenovirus (0.86 ± 0.42 × 106; n = 9). LIGHT is critical for optimal CD4+ T cell alloresponses in MHC class II-disparate MLC and GVHD.",
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T1 - IL-12-independent LIGHT signaling enhances MHC class II disparate CD4 + T cell alloproliferation, IFN-γ responses, and intestinal graft-versus-host disease

AU - Brown, Geri R.

AU - Lee, Edward L.

AU - El-Hayek, Jihad

AU - Kintner, Katherine

AU - Luck, Cheryl

PY - 2005/4/15

Y1 - 2005/4/15

N2 - Inhibition of LIGHT (a cellular ligand for herpes virus entry mediator and lymphotoxin receptor)/herpes simplex virus entry mediator (HVEM) and LIGHT/lymphotoxin β receptor (LTβR) interactions decreases mortality in MHC class I and II disparate graft-vs-host disease (GVHD). The present studies assessed the effects of these interactions on the generation of CD4 + T cell alloresponses in MHC class II-disparate MLC and GVHD. An inhibitor protein of LIGHT and LTαβ2 (LTβR-Ig) and an inhibitor protein of LIGHT (HVEM-Ig) caused similar decreases in alloresponses of control B6 or B6.129S1-IL12rb2tm1Jm (B6.IL12R-/-) spleen cells (SpC) in a MHC class II-disparate MLC. GVHD-induced wasting disease in MHC class II-disparate recipients of B6 CD4+ SpC who received either the LTβR-Ig-encoding adenovirus (LTβR-Ig Adv; 13.1 ± 10.9%; n = 10; p = 0.0004) or the HVEM-Ig-encoding adenovirus (HVEM-Ig Adv; 16.4 ± 9.9%; n = 13; p = 0.0008) was significantly reduced compared with that in recipients of a control adenovirus (30.4 ± 8.8%; n = 13). Furthermore, gut GVHD histologic scores of recipients of B6 CD4+ SpC who received the LTβR-Ig Adv (0.8 ± 0.8; n = 5; p = 0.0007) or the HVEM-Ig Adv (1.4 ± 0.5; n = 5; p = 0.008) were reduced compared with scores of recipients of a control adenovirus (2.5 ± 0.75; n = 11). In the intestine, both LTβR-Ig Adv and HVEM-Ig Adv decreased CD4+ T cells (0.35 ± 0.4 × 106 (n = 6) vs 0.36 ± 0.02 × 106 (n = 9); p = 0.03 and p = 0.007) compared with control adenovirus (0.86 ± 0.42 × 106; n = 9). LIGHT is critical for optimal CD4+ T cell alloresponses in MHC class II-disparate MLC and GVHD.

AB - Inhibition of LIGHT (a cellular ligand for herpes virus entry mediator and lymphotoxin receptor)/herpes simplex virus entry mediator (HVEM) and LIGHT/lymphotoxin β receptor (LTβR) interactions decreases mortality in MHC class I and II disparate graft-vs-host disease (GVHD). The present studies assessed the effects of these interactions on the generation of CD4 + T cell alloresponses in MHC class II-disparate MLC and GVHD. An inhibitor protein of LIGHT and LTαβ2 (LTβR-Ig) and an inhibitor protein of LIGHT (HVEM-Ig) caused similar decreases in alloresponses of control B6 or B6.129S1-IL12rb2tm1Jm (B6.IL12R-/-) spleen cells (SpC) in a MHC class II-disparate MLC. GVHD-induced wasting disease in MHC class II-disparate recipients of B6 CD4+ SpC who received either the LTβR-Ig-encoding adenovirus (LTβR-Ig Adv; 13.1 ± 10.9%; n = 10; p = 0.0004) or the HVEM-Ig-encoding adenovirus (HVEM-Ig Adv; 16.4 ± 9.9%; n = 13; p = 0.0008) was significantly reduced compared with that in recipients of a control adenovirus (30.4 ± 8.8%; n = 13). Furthermore, gut GVHD histologic scores of recipients of B6 CD4+ SpC who received the LTβR-Ig Adv (0.8 ± 0.8; n = 5; p = 0.0007) or the HVEM-Ig Adv (1.4 ± 0.5; n = 5; p = 0.008) were reduced compared with scores of recipients of a control adenovirus (2.5 ± 0.75; n = 11). In the intestine, both LTβR-Ig Adv and HVEM-Ig Adv decreased CD4+ T cells (0.35 ± 0.4 × 106 (n = 6) vs 0.36 ± 0.02 × 106 (n = 9); p = 0.03 and p = 0.007) compared with control adenovirus (0.86 ± 0.42 × 106; n = 9). LIGHT is critical for optimal CD4+ T cell alloresponses in MHC class II-disparate MLC and GVHD.

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